What is the evidence that a pharmacy team working in an acute or emergency medicine department improves outcomes for patients: A systematic review

Abstract Pharmacy services within hospitals are changing, with more taking on medication reconciliation activities. This systematic review was conducted to determine the measured impacts of Pharmacy teams working in an acute or emergency medicine department. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and was prospectively registered on PROSPERO, National Institute for Health and Care Research, UK registration number: CRD42020187487. The systematic review had two co‐primary aims: a reduction in the number of incorrect prescriptions on admission by comparing the medication list from primary care to secondary care, and a reduction in the severity of harm caused by these incorrect prescriptions; chosen to determine the impact of pharmacy‐led medication reconciliation services in the emergency and acute medicine setting. Seventeen articles were included. Fifteen were non‐randomized controlled trials and two were randomized controlled trials. The number of patients combined for all studies was 7630. No studies included were based within the UK. All studies showed benefits in terms of a reduction in medicine errors and patient harm, compared to control arms. Nine articles were included in a statistical analysis comparing the pharmacy intervention arm with the non‐pharmacy control arm, with a Chi2 of 101.10 and I 2 value = 92%. However, studies were heterogenous with different outcome measures and many showed evidence of bias. The included studies consistently indicated that pharmacy services based within acute or emergency medicine departments in hospitals were associated with fewer medication errors. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings including out‐of‐hours working.


| INTRODUC TI ON
Medication use is almost ubiquitous in the prevention, treatment, and management of disease. 1

NHS Digital identified that in England
the 2019-2020 medication spend was listed as £20.9 billion with around £11.7 billion being spent on the medication used in hospitals. 2 Therapy options have become more complex across all disease areas and multi-morbidity is increasing in our aging population. This has resulted in high levels of polypharmacy (defined as the concurrent use of multiple medication items by one individual 3 ). The 2021 Ridge report described that 15% of people in England are taking more than five medications a day, with 7% on more than eight medications a day. 4 Medication errors have been defined as patient safety incidents where an error has occurred in the process of prescribing, administering, monitoring, or providing advice on medication. They can be divided into two categories: errors of commission or errors of omission. 5 The former includes the wrong medicine or dose being given.
The latter is when a dose or medication is missed or monitoring is not implemented. 6 Research reviewed by NHS England has suggested an error rate of 7% within a hospital setting and 5% within general practice, 6 indicating that medication errors are common.
Adverse drug reactions (ADRs) are defined as appreciably harmful or unpleasant reactions resulting from an intervention related to the use of a medication product 7 and problematic polypharmacy is defined as the inappropriate prescribing of multiple medication. 3 These are thought to occur in 10%-20% of in-patient hospital admissions 5 and negatively impact patient care, increasing hospital length of stay and overall NHS costs. 4 ADRs are more common in the presence of problematic polypharmacy.
The transfer of care between care providers is an area of high risk for medication errors. It had been estimated that 30%-70% of patients had an error or unintentional change to their medication during transitions from acute services. 8 The reasons for these errors are complex but may reflect current limitations within data sharing across prescribing systems. 4 Also, transitions of care are most often made during an emergency or unplanned healthcare event (such as the transition from primary care or care home to hospital emergency departments). These tend to be busy areas of clinical service, with patients being seen by multiple health staff, who are caring for many patients at the same time. There were 25 million Emergency Department attendances in 2019/20 with an increase of 24% between 2011/12 and 2020/ 21. 9 It is unlikely that the increasing demand for acute services and acute transitions of care will abate, and new strategies are needed to reduce medication errors, including more effective use of the clinical multi-disciplinary team.
Medication reconciliation is the process of identifying an accurate list of a person's current medications and comparing them with the current list in use. 1 This includes any treatments supplied through additional healthcare providers and over-the-counter or complementary medication. Once discrepancies are identified, they should be resolved promptly. The National Institute for Health and Care Excellence (NICE), advises that medicine reconciliation should be completed within 24 h or sooner if clinically necessary when a person moves from one care setting to another. 1 A number of systematic reviews and meta-analyses have identified the benefits of pharmacy-led medication review reducing but not eradicating medicine errors within the emergency department, 10 transitions of care between secondary and primary care, 11,12 and the low-level impact on hospital readmissions. 13 However, of these few have been conducted in both an acute/emergency setting, and none have specifically assessed the impact of a pharmacy team aiding with medication histories and reconciliation during acute medical admissions. This SR was conducted to determine the outcome of a Pharmacy team working in an acute or emergency medicine department.

| Protocol and registration
The systematic review protocol was made using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, UK) guideline 14 and the Cochrane Handbook guidance, UK. 15 It was registered on PROSPERO, NIHR, UK (registration number: CRD42020187487-see https://www.crd.york.ac.uk/prosp ero/ displ ay_record.php?Recor dID=187487).

| Study design
Studies were selected on the inclusion and exclusion criteria described in Table 1.

| Outcomes
The co-primary outcomes were.

A reduction in medication errors, defined as errors in med-
ication reconciliation; errors in medication prescribing (dose, formulation, frequency, type of administration); errors in medication transcription (inclusive of commissions (unintentional new medications) or omissions (unintentionally missed medications)); medication interactions; a failure of appropriate dose adjustment for patient characteristics (age, weight, organ function).

2.
A reduction in patient harm, defined as a statistically significant risk reduction value.
If data were available, a subgroup analysis was planned to assess the impact of the interventions on the speed of processing patients through the acute healthcare service, whether staff experience (seniority grade) affected the number of errors identified and whether polypharmacy and multimorbidity affected medication error rates.

| Study selection
Each paper was independently reviewed by at least two authors (EP and AC/NA), and disagreements were resolved by discussions with a third reviewer. Reasons for inclusion or exclusion were documented.
After the initial screening, articles were exported into EndNote X9® (Clarivate) for full-text screening. Results were then exported to Microsoft Excel® (Microsoft) for review. Two authors (EP and AC/ NA) read through the full articles using the predefined inclusion and exclusion criteria, disagreements were resolved via a discussion with a third reviewer, and reasons for outcomes were noted.

| Data extraction
A standardized form for data synthesis was built and piloted before use. The data were synthesized using this standardized form by the first author (EP). Duplicate records were removed and the reason for exclusion was recorded. The articles were divided and checked TA B L E 1 Inclusion and exclusion criteria for the systematic review

Inclusion
Exclusion: Set within an acute or emergency medicine department Any studies not assessing a pharmacy service The intervention consisted of a pharmacy service (being provided by pharmacists, clinical pharmacy technicians, pre-registration pharmacists, or pharmacy students) Those which had no clear non-pharmacy control for the medication history or reconciliation intervention to be measured parallel to There was no restriction by medical or surgical condition Outcomes not associated with medication discrepancies The pharmacy service consisted of a full medication history or reconciliation, in comparison to the control of having no pharmacy service Studies not set within an acute medicine or an emergency medicine hospital department There were no restrictions on age Case studies were excluded, and any case series with less than 10 participants Studies using other services or whose focus was solely reviewing the impact of medication-taking tools were excluded during this review Previous systematic reviews and meta-analyses were excluded in the full data analysis. (The findings of existing systematic reviews and meta-analyses were discussed within the discussion section. Primary studies from these reviews were searched and included if these met the inclusion criteria.) Note: Criteria are also available on PROSPERO (registration number: CRD42020187487 -see https://www.crd.york.ac.uk/prosp ero/displ ay_record. php?Recor dID=187487).
between two authors (AC/NA) to check for inaccuracies. Any disagreements with missing data were resolved by discussion with a third reviewer. Each tool was applied by one author (AC/NA) and checked by a second author (EP). Any queries with missing data were resolved by discussion by a third author.

| Data synthesis
RevMan® (Cochrane, UK) 20 was used to combine the data and perform statistical analysis. Heterogeneity between studies was reviewed using a visual inspection of the forest plot: Chi 2 test and I 2 tests were also completed. Where data were limited, descriptive analyses were used.

| RE SULTS
Of the 2110 eligible citations (once duplicates were removed), 65 met the inclusion criteria, as shown in the PRISMA® UK flow diagram ( Figure 1). When full-text articles were assessed, a further 48 were excluded, leaving 17 articles for inclusion.
Of the 17 articles that were included in the qualitative synthesis, nine articles were used in the subgroup statistical analysis, owing to a high level of heterogeneity across the 17 articles.
Of the included studies, 15 were non-randomized controlled trials (NRCTs) [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and two were randomized controlled trials (RCT), 36,37 all of which were available in English.  Table 2 provides an overview of all studies within the review.  or omissions (unintentionally missed medications). Figure 4 shows the forest plot and Figure 5 shows the funnel plot for this outcome across included studies with the calculated risk ratio. Whilst the Chi 2 test showed statistical significance, the data were highly heterogeneous. The I 2 value was reported at 92% and showed considerable variation across studies, owing to study heterogeneity. The funnel plot indicates there may have been publication bias.

| Inappropriate dose adjustments for patient characteristics on admission
Dose adjustments were not reported as an investigated outcome in both the control and intervention arms within any of the studies.

| Reduction in patient harm
Reduction in patient harm was extracted as a primary co-outcome from the studies using pre-defined criteria from each study. The outcome was only reported in seven of the 17 included studies ( Only two studies had an independent group of staff assessing the severity of the errors. 24

Control (C) and intervention (I) Outcomes overall Results control (C) and Intervention (I)
Excluded if scheduled for discharge on the same day, unable to answer the questions needed to complete the study, were unable to communicate due to language difficulties, were under psychiatric care, had a medical record of dementia or confusion, and/or were unable to give their consent  (97/554 errors in total in the control group) extreme and high harm. −1% (6/595 errors in total in the intervention group) and 11.6% (64/554 errors in total in the control group) moderate harm.
Medication discrepancies and severity.

Medication errors during reconciliation -Patients with at least one unintended discrepancy was reduced from 59% (29/49 (C)) to 10.5% (8/76 (I)) (p < .001). Errors as a percentage of medication errors within each arm.
− 42% (73/174 errors out of the recorded prescriptions total) control -3.5% (11/315 errors out of the recorded prescriptions total) intervention -The overall discrepancy rate was 0.68 per patient (SD 1.28); it was 1. Patients were included in the study if they were admitted through the main community teaching hospital ED and were taking 1 or more medications.

| 15 of 24
PUNJ et al. for the pharmacy intervention arm to complete the medication history compared to the 9.6 min (range 6-13 min) in the control arm.

| The effect of Pharmacy staff experience on the pharmacy service provided
None of the studies reported the seniority of pharmacy professionals.

| The effect of Multimorbidity and polypharmacy on patients' risk of experiencing medication errors
None of the studies reported the impact of multi-morbidity or polypharmacy.

| DISCUSS ION
To the authors' knowledge, this is the first systematic review assessing the impact of pharmacy services across both acute and F I G U R E 2 Cochrane Risk of bias tool (ROB2® Cochrane, UK) applied to the randomized controlled trials. The two studies included were randomized controlled trials. F I G U R E 5 Funnel plot of the effects of a pharmacy intervention versus the control arm for providing a medication history on admission to an acute or emergency medicine department, for nine studies. [22][23][24]26,29,32,[34][35][36] Each dot represents one study. A positive outcome would be the equal distribution of studies, with those which were larger (with more power) being at the top. The x-axis shows the 95% confidence interval (CI) of the risk ratio. For this review, this is the risk of a medication error happening in the pharmacy intervention group compared to the control group. The y axis shows the standard error of the effect measure.

| Strengths and weaknesses
The strengths of this review included the similarity of the results of the studies. Each described the benefit of a pharmacy team reducing medication errors within an emergency department and during transitions of care. 10,11,13  1.8% (1/57 errors in total in the intervention group) and 5.8% (10/171 errors in total in the control group) potentially resulting in severe discomfort or clinical deterioration.
Note: The severity scales used were defined within the table.

TA B L E 3 (Continued)
admitted to either the acute or emergency departments, performed using standard methodologies with a protocol completed and published prior to review commencement.
The limitations of this review were that study heterogeneity and differences in the metrics that were reported resulted in a narrative review for many studies, with a statistical analysis only possible in a subgroup rather than a quantitative meta-analysis. Some of the smaller studies included within this review may have bias associated with their results, as effect size can be overestimated in studies that include smaller populations. Studies may have been affected by confounding variables for example the recruitment of patients was mainly during the day and on weekdays rather than on a weekend or at night. For some studies, this had been noted in the inclusion criteria [22][23][24][25]28,29,[31][32][33][34]37 but there was no comparison or reference to the recruitment of participants out-of-hours. The statistical subgroup analysis of the studies was performed on less than 50% of the articles consisting of 3001 patients. One of the main limitations of this review is that all studies included were set outside of the UK, either within Europe or internationally. As a result, the generalisability of these results to the UK NHS may be limited, owing to the data being reported from places that may have private healthcare systems. Further studies are needed that assess UK health settings prior to service modification.
The studies presented within this systematic review indicate that medication reconciliation services provided by pharmacy staff decrease the number of medication discrepancies. However, there are several uncertainties that remain which would benefit from further research. The full benefit of a pharmacy service out of hours is unclear.
It is also unclear whether benefits would be greater if targeted, for example, to those with complex care needs or polypharmacy. As highlighted in a recent report by Ridge., 2021 4 the pharmacy workforce might be best placed to support medication optimization and deprescribing within hospitals. It would be beneficial to examine services that move from following up errors retrospectively, to proactively, preventing these within both the emergency and acute departments. 22

| CON CLUS ION
The studies included within this systematic review consistently indicate that pharmacy services based within the acute and emergency medicine departments in hospitals are associated with fewer medication errors.
However, these results should be interpreted with caution as studies were affected by bias, heterogenous in design, and often included unblinded assessments of efficacy. All studies were set outside of the UK and differences in healthcare models might impact the results, meaning that studies might need to be replicated in specific UK settings to determine whether the model of care should be adjusted. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings. However, to date, the evidence indicates that pharmacy services providing medicine reconciliation at the point of admission to the hospital reduce medicines errors and that these services should be assessed in more detail.
Conventionally, pharmacists have not been deployed within emergency departments, but this is changing. Patients are spending considerable time within ED, and it is recognized that patients using ED are increasingly complex with significant polypharmacy.
There are known patient harm from missing regular medications, as described within this systematic review. Currently, there is variation in the type of pharmacy services that exist nationally within Emergency and Acute Medicine departments, and often limited funding is available for these services. Future research should assess best practices and service models which improve flow and increase patient safety, including pharmacy team reviews earlier in the admission, focusing services on more complex patients, and outof-hours work.

CO N FLI C T O F I NTE R E S T
ES reports grants from HDR-UK, during the conduct of the study; grants from Medical Research Council, grants from NIHR, grants from Wellcome Trust, grants from British Lung Foundation, and grants from Alpha 1 Foundation, outside the submitted work.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author.

E TH I C S A PPROVA L S TATE M E NT
As a systematic review of published literature, no specific ethical approvals were needed.